Cell-based Assay Protocol for the Prognostic Prediction of Idiopathic Scoliosis Using Cellular Dielectric Spectroscopy

Akoume, Marie-Yvonne; Franco, Anita; Moreau, Alain

doi:10.3791/50768

Cited by 6 publications

(6 citation statements)

References 15 publications

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“…In this study, we are proposing the first hypothesis relating brace outcome and intrinsic cellular profile connected to the roles of GPCRs as mechanosensors. This study evaluated patient outcomes based on three biological endophenotypes defined by the differential hypofunctionality of Gi alpha subunits [10,11] as initially evidenced by a differential dysfunction of melatonin signal transduction [7][8][9]. Differences between the three endophenotypes acquired through a cell-based assay were identified in the outcomes of brace treatment both for final Cobb and progression criteria.…”

Section: Discussionmentioning

confidence: 99%

“…All participants were classified according to their biological endophenotype, FG1, FG2, or FG3. The endophenotypes were measured by CDS using PBMCs as previously described [9,10].…”

Section: Cellular Dielectric Spectroscopy (Cds) Assaymentioning

confidence: 99%

“…In complex multifactorial disorders, such as AIS, biological endophenotypes have the potential utility both in identifying risk genes and in enlightening the pathophysiology. We previously identified three distinct biological endophenotypes for AIS based on a differential protein G inhibitory (Gi) signaling dysfunction in AIS patients [7][8][9][10][11]. These observations led to the classification of patients into three biological endophenotypes or "functional groups" (referred to as FG1, FG2, and FG3), based on the maximal Gi response observed after Gi alpha subunits stimulation [11].…”

Section: Introductionmentioning

confidence: 99%

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Patient outcomes in idiopathic scoliosis are associated with biological endophenotypes: 2020 SOSORT award winner

et al. 2020

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Purpose Bracing is the treatment of choice for idiopathic scoliosis (IS), unfortunately factors underlying brace response remain unknown. Clinicians are currently unable to identify patients who may benefit from bracing, and therefore, better molecular stratification is critically needed. The aim of this study is to evaluate IS patient outcomes at skeletal maturity in relation to biological endophenotypes, and determine specific endophenotypes associated to differential bracing outcomes. This is a retrospective cohort with secondary cross-sectional comparative studies. Methods Clinical and radiological data were collected from 563 IS patients, stratified into biological endophenotypes (FG1, FG2, FG3) based on a cell-based test. Measured outcomes were maximum Cobb angle at skeletal maturity, and if severe, spinal deformity (≥ 45°) or surgery was attained. Treatment success/failure was determined by standard progression thresholds (Cobb ≥ 45° or surgery; Cobb angle progression ≥ 6°). Multivariable analyses were performed to evaluate associations between endophenotypes and clinical outcome. Results Higher Cobb angles at maturity for FG1 and FG2 patients were observed (p = 0.056 and p = 0.05), with increased likelihood of ≥ 45° and/or surgery for FG1 (OR = 2.181 [1.002-4.749] and FG2 (OR = 2.141 [1.038-4.413]) compared to FG3. FG3 was 9.31 [2.58-33.61] and 5. 63 [2.11-15.05] times more likely for bracing success at treatment termination and based on the < 6° progression criterion, respectively, compared to FG1. Conclusion Associations between biological endophenotypes and outcomes suggest differences in progression and/or bracing response among IS patients. Outcomes were most favorable in FG3 patients. The results pave the way for establishing personalized treatments, distinguishing who may benefit or not from treatment.

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Section: Discussionmentioning

confidence: 99%

“…All participants were classified according to their biological endophenotype, FG1, FG2, or FG3. The endophenotypes were measured by CDS using PBMCs as previously described [9,10].…”

Section: Cellular Dielectric Spectroscopy (Cds) Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Patient outcomes in idiopathic scoliosis are associated with biological endophenotypes: 2020 SOSORT award winner

et al. 2020

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“…Several previous studies have reported that different characteristics can be used for the prediction of severe spine deformity, such as clinical [ 27 ], radiographic [ 28 ], physiologic [ 29 ], biochemical [ 30 ], genetic [ 31 ], and combinatorial parameters [ 32 ]. Tan et al [ 21 ] examined 186 AIS patients and noted that curve magnitude more than 30 degrees at first session was the most important predictive factor for curve progression.…”

Section: Discussionmentioning

confidence: 99%

High Ghrelin Level Predicts the Curve Progression of Adolescent Idiopathic Scoliosis Girls

Zhang

Zhou

et al. 2018

BioMed Research International

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Background Adolescent idiopathic scoliosis (AIS) is common deformity with unknown cause. Previous studies have suggested the abnormal serum leptin and ghrelin level in AIS girls. The aim of present study was to evaluate whether the serum leptin and ghrelin level could serve as risk factor in predicting the curve progression in AIS girls. The associations between them and the physical characteristics were also investigated. Materials and Methods Circulating leptin and ghrelin levels from 105 AIS girls and 40 age-matched non-AIS girls were examined by enzyme-linked immunosorbent assay. The correlations between ghrelin and leptin levels and growth-related parameters (age, weight, corrected height, corrected BMI, main Cobb angle, and Risser sign) were analyzed in AIS group. Multivariate logistic regression was used to investigate factors predicting curve progression in AIS girls. Results A significantly lower leptin level (6.55 ± 2.88 vs. 8.01 ± 3.12 ng/ml, p < 0.05) and a higher ghrelin level (6.33 ± 2.46 vs. 4.46 ± 2.02 ng/ml, p < 0.05) were found in all AIS patients, as compared with normal controls. Curve progression patients had a higher ghrelin level than stable curve patients (7.61 ± 2.48 vs. 5.54 ± 2.11 ng/ml, p < 0.01); for leptin level, there was no significant difference between progression and stable group. The results of multivariate logistic stepwise regression showed that premenarche status, initial main Cobb magnitude that was more than or equal to 23°, high ghrelin level (≥7.30 ng/ml), and lower Risser grade (grades 0 to 2) were identified as risk factors in predicting curve progression. Ghrelin levels of >6.48 ng/ml were predictive for curve progression with 70.00 % sensitivity and 72.31 % specificity, and the area under the curve (AUC) was 0.741 (95 % confidence interval 0.646-0.821). Conclusions High ghrelin level may serve as a new quantitative indicator for predicting curve progression in AIS girls.

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“…Ghrelin secretion is stimulated by several Gs-coupled receptors and inhibited by many Gicoupled and Gq receptors [31]. Given that a Gisignalling dysfunction has been reported in AIS [32], it is conceivable that Gi protein hypofunctionality in AIS could contribute to the elevation of plasma ghrelin levels in AIS patients.…”

Section: Discussionmentioning

confidence: 99%

Fasting total ghrelin levels are increased in patients with adolescent idiopathic scoliosis

Gennero¹,

Conte-Auriol²,

Mus³

et al. 2013

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Background: A control study was designed to investigate circulating Ghrelin levels in adolescent girls with adolescent idiopathic scoliosis (AIS) and controls. Eating behavioral disorders, endocrine disorders, abnormal growth pattern and osteopenia have been well documented in AIS. Ghrelin is an orexigenic hormone produced by the stomach which reflects body weight changes and stimulates growth hormone secretion. Recently, it has been shown to be associated with bone metabolism and eating behavior. However, the circulating levels of ghrelin have never been evaluated in AIS patients. Methods: Forty nine AIS girls and 15 controls were included. Anthropometric parameters and fasting circulating total ghrelin were measured. Curve severity was evaluated in AIS girls. The relationships between ghrelin and age, body weight, height, body mass index (BMI), BMI Z-score and corrected anthropometric parameters were analyzed in AIS girls and controls. Results: There was no significant difference in body weight, height, BMI or BMI Z-score between AIS and controls. Serum ghrelin level was 1.8 fold higher in AIS girls than in controls. Elevation of ghrelin levels remained significant when corrected BMI or corrected BMI Z-score were considered. Unlike in controls, positive correlations were found between ghrelin and age in AIS girls with a gradual increase of circulating ghrelin with age. Conclusions: We have observed significantly higher circulating ghrelin levels in AIS than in controls with a positive correlation with age. This pilot-study suggests that ghrelin signaling might play a role in the initiation or development of AIS. Further studies are needed to validate theses results.

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Cell-based Assay Protocol for the Prognostic Prediction of Idiopathic Scoliosis Using Cellular Dielectric Spectroscopy

Cited by 6 publications

References 15 publications

Patient outcomes in idiopathic scoliosis are associated with biological endophenotypes: 2020 SOSORT award winner

Patient outcomes in idiopathic scoliosis are associated with biological endophenotypes: 2020 SOSORT award winner

High Ghrelin Level Predicts the Curve Progression of Adolescent Idiopathic Scoliosis Girls

Fasting total ghrelin levels are increased in patients with adolescent idiopathic scoliosis

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